title: Efficacy of CMX001 as a prophylactic and presymptomatic antiviral agent in New Zealand white rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans.
abstract: CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to smallpox virus vaccinations. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. amandar@ufl.edu
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Rice
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Adams
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lampert
authors.forename: Scott
authors.initials: S
authors.lastname: Foster
authors.forename: Alice
authors.initials: A
authors.lastname: Robertson
authors.forename: George
authors.initials: G
authors.lastname: Painter
authors.forename: Richard W
authors.initials: RW
authors.lastname: Moyer
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D023482:Bioterrorism; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D006801:Humans; D045908:Mpox, Monkeypox / Q000188:drug therapy / Q000517:prevention & control; D063065:Organophosphonates / Q000008:administration & dosage*; D011817:Rabbits; D012899:Smallpox / Q000188:drug therapy / Q000517:prevention & control; D012900:Smallpox Vaccine / Q000009:adverse effects; D014616:Vaccinia virus / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D012900:Smallpox Vaccine; C525733:brincidofovir; D003596:Cytosine